Pre-treatment effect of myo-inositol and l-5, methyltetrahydrofolate in ovulation induction oocyte quality and pregnancy outcome in clomiphene resistance polycystic ovarian disease


  • Ankit Bhardwaj Department of Pharmacology, SIMS, Hapur, Uttar Pradesh, India
  • Anand Shukla Department of Pharmacology, SIMS, Hapur, Uttar Pradesh, India
  • Sunita Singh Department of Pharmacology, SIMS, Hapur, Uttar Pradesh, India
  • Rajni Agarwal Department of Obstretics and Gynaecology, SIMS, Hapur, Uttar Pradesh, India



Myo-inositol, L-5 methyltetrahydrofolate, Polycystic ovarian syndrome


Background: This study was designed to assess the treatment effect of myo-inositol and l-5, methyltetrahydrofolate in oocyte quality, pregnancy outcome in clomiphene citrate resistance PCOS cases.

Methods: Authors conducted prospective open label, randomized, parallel group study in SIMS Hapur, U.P. Eligible patients full filling inclusion criteria were randomized into two groups having 25 patients in each group using myo-inositol 580mg and l-5, methyltetrahydrofolate 800mcg in treatment group and tab folic acid 400mcg in placebo group for 12 weeks. The follow-up visits are on weeks 4, 8 and 12.

Results: 12 weeks later, 21 patients in treatment group restored one spontaneous menstrual cycle and 19 patients maintained the normal ovulatory activity in follow up cycle. Ovulation induction done in 18 patients with clomiphene citrate at the dose of 50mg during treatment out of which 10 conceive, as compared with only 9 women out of the 25 women (36 percent) in the placebo group ovulate (P>0.001) out of which 4 conceived. There was significant decrease in Sr. testosterone, DHEA and AMH level and estradiol level, while statically significant increase in Sr. SHBG and FSH level seen in treatment group(p<0.001).

Conclusions: In the study, more number of studied patients get back to normal menstrual cyclicity, insulin-lowering activity and its intracellular role in oocyte maturation. Significant Dec seen in serum estradiol level at the day of HCG administration.


The Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19:41-7.

Zawadski JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens JR, Haseltine F, editors. Polycystic ovary syndrome. Boston: Blackwell Scientific; 1992:377-384.

Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. Criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an androgen excess society guideline. The Journal of Clinical Endocrinology & Metabolism. 2006 Nov 1;91(11):4237-45.

Hourvitz A, Machtinger R, Maman E, Baum M, Dor J, Levron J. Assisted reproduction in women over 40 years of age: how old is too old? Reprod Biomed Online. 2009;19:599-603.

Wiener-Megnanzi Z, Vardi L, Lissak A, Shnizer S, Reznick AZ, Ishai D, et al. Oxidative stress indices in follicular fluid as measured by the thermochemiluminescence assay correlate with outcome parameters in in vitro fertilization. Fertil Steril. 2004;82(3):1171-6.

Steegers-Theunissen RP, Boers GH, Blom HJ, Trijbels FJ, Eskes TK. Hyperhomocysteinemia and recurrent spontaneous abortion or abruptio placentae. Lancet 1992;339(8801):1122-3.

Wouters MG, Boers GH, Blom HJ, Trijbels FJ, Thomas CM, Borm GF, et al. Hyperhomocysteinemia: a risk factor in women with unexplained recurrent early pregnancy loss. Fertil Steril. 1993;60:820-5.

Hague WM. Homocysteine and pregnancy. Best Pract Res Clin Obstet Gynaecol. 2003;17:459-69.

Refsum H, Smith AD, Ueland PM, Nexo E, Clarke R, Mcpartlin J, et al. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem. 2004;50:3-32.

Boxmeer JC, Brouns RM, Lindemans J, Steegers EA, Martini E, Macklon NS, et al. Preconception folic acid treatment affects the microenvironment of the maturing oocyte in humans. Fertil Steril. 2008;89:1766-70.

Chiu TT, Rogers MS, Law Elk, Briton- CM, Cheung LP, Haines CJ. Follicular fluid and serum concentrations of myo-inositol in patients undergoing IVF: relationship with oocyte quality. Hum Reprod. 2002;17:1591-6.

Chiu TT, Rogers MS, Briton-Jones C, Haines C. Effect of myo-inositol on the in-vitro maturation and subsequent development of mouse oocytes. Hum Reprod. 2003;18:408-16.

Chiu TT, Tam PP. A correlation of the outcome of clinical in vitro fertilization with the inositol content and embryotrophic properties of human serum. Journal of assisted reproduction and genetics. 1992 Dec 1;9(6):524-30.

Papaleo E, Unfer V, Baillargeon JP, Fusi F, Occhi F, DE Santis L. Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. Fertil Steril. 2009;91:1750-4.

Fahy MM, Kane MT. Incorporation of [3H] inositol into phosphoinositides and inositol phosphates by rabbit blastocysts. Mol Reprod Dev. 1993;34:391-5.

Holm P, Booth PJ, Schmidt MH, Greve T, Callesen H. High bovine blastocyst development in a static in vitro production system using SOFaa medium supplemented with sodium citrate and myo-inositol with or without serum-proteins. Theriogenology. 1999;52:683-700.

Berridge MJ, Irvine RF. Inositol phosphates and cell signalling. Nature. 1989 Sep;341(6239):197.

Sirmans SM, Pate KA. Epidemiology, diagnosis and management of polycystic ovary syndrome. Clinical Epidemiology. 2014;6:1-13.

Unfer V, Nestler JE, Kamenov ZA, Prapas N, Facchinetti F. Effects of Inositol(s) in women with PCOS: a systematic review of randomized controlled trials. International journal of Endocrinology. 2016:1849162.

Nehra J, Kaushal J, Singhal SR, Ghalaut VS. A comparative study of efficacy and safety of myo-inositol versus metformin in polycystic ovarian syndrome in women. World Journal of Pharmacy and Pharmaceutical Sciences. 2016;5(5):884-96.

Hu L, Shen H, Wu QF, Tian L, Hu MH. Treatment of polycystic ovarian syndrome with insulin sensitizer. Clinical Experimental Obstetrics and Gynaecology. 2014;41:288-92.

Legro RS, Castracane VD, Kauffman RP. Detecting insulin resistance in polycystic ovary syndrome: purposes and pitfalls. Obstetrical and Gynecological Survey. 2004;59:141-54.

Agarwal A, Saleh RA, Bedaiway MA. Role of reactive oxygen species in the pathophysiology of human reproduction. Fertil Steril. 2003;79:829-43.

Pesty A, Avazeri N, Lefevre B. Nuclear calcium release by InsP3‐receptor channels plays a role in meiosis reinitiating in the mouse oocyte. Cell Calcium. 1998;24:239-51.




How to Cite

Bhardwaj, A., Shukla, A., Singh, S., & Agarwal, R. (2018). Pre-treatment effect of myo-inositol and l-5, methyltetrahydrofolate in ovulation induction oocyte quality and pregnancy outcome in clomiphene resistance polycystic ovarian disease. International Journal of Basic & Clinical Pharmacology, 7(3), 532–536.



Original Research Articles